β-glucan primed and DYDGP microparticles treatment induces trained immunity against mycobacterium tuberculosis infected human macrophage: an in-vitro/in-vivo studies

Abstract Background Tuberculosis (TB) remains a persistent global health challenge, prompting the exploration of innovative strategies to enhance prevention and treatment outcomes. Host-directed therapies have emerged as a promising avenue in TB management, potentially reshaping current treatment paradigms. This study investigates the efficacy of β-glucans as immune-training agents to strengthen the host's defense mechanisms against Mycobacterium tuberculosis infection. Methods Our investigation focuses on DYDGP-treated, trained cells to elucidate the effects of β-glucans on immune training. We assessed the integrity of trained macrophage cell membranes and their enhanced phagocytic uptake compared to untrained cells. Additionally, we examined the activation of crucial cellular signalling pathways, enhanced oxidative reactive oxygen species (ROS) production, and acidic vesicular organelles formation within infected and trained macrophage cells at the 24-hour mark. In-vivo and in-vitro phagocytosis uptake assays were conducted to evaluate the impact of training on phagocytic activity, while lysotracker staining data provided insights into macrophage immune responses and pathogen clearance. Furthermore, we investigated the modulatory effects of DYDGP-treated β-glucans on functional characteristics, such as enhanced mycobacterial control at 24 hours, confirmed by colony-forming unit (CFU) assays. Results Our findings demonstrate promising outcomes, with trained macrophage cells exhibiting intact cell membranes and enhanced phagocytic uptake compared to untrained cells. β-glucans effectively activate crucial cellular signalling pathways, leading to enhanced oxidative ROS production and acidic vesicular organelles formation within infected and trained macrophage cells at 24 hours. In vivo and in vitro assays reveal that training enhances phagocytosis of particles and induces a potent immune response, resulting in enhanced phago-lysosomal maturation and pathogen clearance within infected and trained macrophage cells at 24 hours. Additionally, DYDGP-treated β-glucans exhibit modulatory effects on functional characteristics, including enhanced mycobacterial control at 24 hours. Conclusions These results underscore the potential of β-glucans as adjunctive therapies in TB management. However, further research is needed to comprehensively elucidate the observed effects and optimize their therapeutic application. This study lays the groundwork for future investigations aimed at harnessing the immunomodulatory properties of β-glucans to combat TB effectively.